Grant: Operating Grant

Campylobacter jejuni (Cj) is the leading cause of bacterial food poisoning in the developed world. Yet, its mechanisms of pathogenesis remain mysterious. Through screening and selection, we have identified means by which this pathogen is so successful. One is its shape. Cj is helical/corkscrew in morphology, and this abets its ability to burrow into the mucosa of both susceptible and commensal hosts. We have, for the first time, identified gene products involved in the cell envelope (peptidoglycan; PG) required for this shape, and logical candidates for further study. Using a rounded genetics and biochemical approach, we will perform gene deletion studies, protein localization, exploration of newly identified factors, investigation of how these factors interact with each other to control helicity, and studies of PG factors involved in the natural shape-change processes of cell division and coccoid formation as the bacteria age. Also through genetic screens, we identified and defined the Cj hyperosmotic stress response. Surprisingly, this revealed significant heterogeneity within wild type Cj 'clones', at a frequency significantly outweighing standard single nucleotide polymorphism and phase-variation. This type of heterogeneity may be what underlies the ability of Cj to infect and survive in so many diverse environments despite fragile growth requirements. We are investigating the role of purine metabolism in this process, exploring a novel regulator, and identifying and characterizing new hypervariable genes. We are excited to continue studies linking this variability with our bacterial cell shape findings, which also yield heterogeneity in a wild type population. Ultimately, we hope that the combination of traditional microbiology, genetics, and biochemistry, together with newer next-gen approaches, will finally provide insight into how and why Cj is such an important human pathogen, and clues to its eradication.